Analysis of NF-B Pathway Proteins in Pediatric Hodgkin Lymphoma: Correlations with EBV Status and Clinical Outcome—A Children's Oncology Group Study
Classical and alternative NF-B pathway activation. (a) Activation of the classical NF-B pathway. Several receptors, including CD30, CD40, and LMP1, induce the classical NF-B pathway by activating the IKK complex. Phosphorylated IKK- phosphorylates IB-, inducing IB polyubiquitination and degradation by the 26S proteasome. Following IB degradation, NF-B dimerizes with NF-B1/p50 and translocates into the nucleus where gene transcription is activated. (b) Activation of the alternative NF-B pathway. The alternative NF-B pathway is activated by a restricted set of cell-surface receptors, including CD30, CD40, and the BAFF receptor. Alternative NF-B pathway activation increases the stability of NIK, which phosphorylates and activates IKK-. IKK- directly phosphorylates NF-B2/p100, inducing partial proteolysis of p100 to p52 by the 26S proteasome. The p52 NF-B subunit dimerizes with Rel-B and translocates into the nucleus, activating gene transcription. Proteins outlined in black were examined in the TMA. Cylindrical structure represents the 26S proteasome.
(a) Classical NF-B activation pathway
(b) Alternative NF-B activation pathway
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